A study published in JAMA Network Open found that the 2025-2026 COVID-19 vaccines were 50% effective against COVID-19-associated emergency department and urgent care visits in adults in the United States. The vaccines showed 55% effectiveness against COVID-19-associated hospitalizations for the same demographic.

Researchers conducted a case-control study using a test-negative design to evaluate interim effectiveness among immunocompetent adults aged 18 years and older. The analysis for emergency department and urgent care encounters included 85,725 adults presenting with COVID-19-like illness. Within this group, 3,941 patients tested positive for SARS-CoV-2 and were considered cases, while 81,784 patients with negative molecular test results served as controls. A total of 9,659 individuals had received a 2025-2026 vaccine before their encounter, with 5% of cases vaccinated compared to 12% of controls. The estimated effectiveness against these encounters was 50% (95% confidence interval [CI], 42%-57%). For adults aged 65 years and older, effectiveness was 48% (95% CI, 37%-56%). The median time since vaccination was 47 days for adults aged 18 and older, and 48 days for those 65 and older.

For the hospitalization analysis, 26,073 adults admitted with COVID-19-like illness were included. This group comprised 1,022 SARS-CoV-2 positive cases and 25,051 molecularly negative controls. Among these patients, 3,140 had received a vaccine dose prior to admission. Vaccinated individuals accounted for 6% of cases and 12% of controls. The estimated effectiveness against hospitalization for adults 18 years and older was 55% (95% CI, 41%-66%) among those vaccinated at least 7 days prior. For adults 65 years and older, the vaccine provided 53% effectiveness (95% CI, 37%-65%). The median time since vaccination was 46 days for both age groups.

Data were obtained from the Virtual SARS-CoV-2, Influenza, and Other Respiratory Viruses Network, an electronic health record-based system including 253 emergency department and urgent care facilities and 179 hospitals across seven states. Eligible encounters occurred between September 3, 2025, and December 31, 2025. The highest number of encounters and hospitalizations occurred during December 2025. Patients were considered vaccinated if they received a dose at least 7 days before the encounter.

The study did not directly account for prior SARS-CoV-2 infection or previous vaccine doses. It did not assess protection over longer periods, against critical illness or death, in children, or in immunocompromised adults.